Spontaneous recurrence of methamphetamine psychosis: process and monoamine neurotransmitter function.

We studied the process that causes a spontaneous recurrence of methamphetamine (MAP) psychosis, a phenomenon known as flashbacks, in 41 female flashbackers by a comparison of clinical characteristics between the 41 flashbackers and 87 non-flashbackers with previous MAP psychosis. We evaluated plasma levels of monoamine metabolites in 25 of the 41 flashbackers, 19 of the 87 non-flashbackers, 9 female patients with persistent MAP psychosis and 61 physically healthy female controls. All 41 flashbackers had experienced a significantly greater frequency of threatening events and threatening paranoid-hallucinatory states than the 87 non-flashbackers during previous MAP abuse. The triggering factor was a mild fear of other persons due to the evocation of frightening images, encoded through threatening experiences during previous MAP abuse. Norepinephrine (NE) levels were significantly associated with a history of flashbacks. Plasma 3-methoxy-4-hydroxyphenylglycol (MHPG) levels were significantly higher during flashbacks and during periods of normalcy in the flashbackers, and in the non-flashbackers, than MHPG levels in the user controls. NE levels in the patients with persistent MAP psychosis were also significantly higher than NE levels in the user controls. Elevated NE levels in the flashbackers were associated with disrupted NE, 5-HT and DA turnover. Thus, MAP-induced sensitization to frightening images may have caused the flashbacks due to aggravated noradrenergic hyperactivity.